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See detailEnhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway
Turlej, Renata K; Fievez, Laurence ULg; Sandersen, Charlotte ULg et al

in Thorax (2001), 56(9), 696-702

As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we ... [more ▼]

As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival. Moreover, because GM-CSF mediates its effects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation. METHODS: Blood granulocytes were recovered from six healthy and six heaves affected horses, a model of asthma. Lung granulocytes were obtained by bronchoalveolar lavage (BAL) from the same horses. Granulocytes were cultured in the presence or absence of anti-GM-CSF receptor antibodies for different times and apoptosis was determined using the Annexin-V/propidium iodide detection method. Nuclear protein extracts from cultured granulocytes were analysed for STAT5 binding activity by electrophoretic mobility shift assay. RESULTS: BAL fluid granulocytes from heaves affected horses demonstrated a significant delay in apoptosis compared with blood granulocytes from the same horses and blood and BAL fluid granulocytes from healthy horses. Conversely, the rate of apoptosis in blood granulocytes from healthy and heaves affected horses was comparable. The enhanced survival of BAL fluid granulocytes from affected horses was suppressed in the presence of antibodies directed against GM-CSF receptors. Increased levels of active STAT5 were found in BAL fluid granulocytes from heaves affected horses and were markedly reduced after treatment with anti-GM-CSF receptor antibodies. CONCLUSIONS: These data indicate that granulocyte survival is enhanced in the lung of heaves affected horses and suggest a role for a GM-CSF activated STAT5 pathway in delaying apoptosis of lung granulocytes in this model of asthma. [less ▲]

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See detailMécanismes de la persistance de l’inflammation chez les chevaux poussifs en rémission
Bureau, Fabrice ULg; Fievez, Laurence ULg; Kirschvink, Nathalie et al

in Proceedings: 27ème Journée de la Recherche Equine (2001)

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See detailTranscription factors in asthma
Bureau, Fabrice ULg

in Proceedings: Basic and Clinical Allergy Meeting (2001)

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See detailEnhanced survival of lung granulocytes in an animal model of asthma : evidence for a role of GM-CSF-activated STAT5 signaling pathway
Turlej, R.; Sandersen, Charlotte ULg; Fievez, Laurence ULg et al

in Proceedings: International Conference of the American Thoracic Society (2001)

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See detailComparison of inulin to urea as dilutional marker of bronchoalveolar lavage in an animal model of asthma
Kirschvink, Nathalie; Fievez, Laurence ULg; Dogné, S. et al

in Proceedings: International Conference of the American Thoracic Society (2001)

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See detailAdaptation to multiday ozone exposure is associated with a failure in granulocytes apoptosis delay
Fievez, Laurence ULg; Kirschvink, Nathalie; Lekeux, Pierre ULg et al

in Proceedings: International Conference of the American Thoracic Society (2001)

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See detailIncreased NF-kB activity in broncho-alveolar lavage cells from an animal model of asthma
Sandersen, Charlotte ULg; Bureau, Fabrice ULg; Turlej, R. et al

in Proceedings: International Conference of the American Thoracic Society (2001)

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See detailOzone adaptation in calves is associated with impaired accumulation of granulocytes in the lung
Fievez, Laurence ULg; Kirschvink, Nathalie; Dogné, S. et al

in Proceedings: Comparative Respiratory Society Meeting (2001)

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See detailConstitutive NF-kappaB activity preserves homeostasis of quiescent mature lymphocytes and granulocytes by controlling the expression of distinct Bcl-2 family proteins
Bureau, Fabrice ULg; Vanderplasschen, Alain ULg; Jaspar, F. et al

in Proceedings: International Symposium: NF-kappaB: Regulation, Gene Expression & Disease (2001)

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See detailp65 homodimer activity in BAL cells is correlated to lung dysfunction in equine heaves
Sandersen, Charlotte ULg; Bureau, Fabrice ULg; Turlej, R. et al

in Proceedings: 2001 World Equine Airways Symposium (2001)

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See detailNF-kB-dependent cytokine production is abolished by cyclopentenone prostaglandins in lung epithelial cells
Bureau, Fabrice ULg

in Proceedings: Annual Congress of the European Respiratory Society (2001)

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See detailSpirometric performance in Belgian Blue calves: I. Effects on economic losses due to the bovine respiratory disease complex.
Bureau, Fabrice ULg; Detilleux, Johann ULg; Dorts, T. et al

in Journal of Animal Science (2001), 79(5), 1301-1304

The aim of this study was to determine whether high spirometric performances in calves are associated with low economic losses due to the bovine respiratory disease complex (BRDC). Five spirometric ... [more ▼]

The aim of this study was to determine whether high spirometric performances in calves are associated with low economic losses due to the bovine respiratory disease complex (BRDC). Five spirometric variables (SV) were measured in 909 double-muscled Belgian Blue calves from 15 to 60 d of age. Afterward, calves were monitored for 6 mo to determine whether they developed BRDC and to determine the costs due to BRDC (i.e., medicine costs and veterinarians' fees, plus estimated financial losses due to mortality in case of death). To analyze the effects of spirometric performances on BRDC cost, a fixed linear model was used for each SV. In addition to SV, each model included the effects of sex, dam's parity, vaccination status, muscular development score, herd-period, and BW. Only herd-period and the maximal ventilation and the vital capacity had significant effects on costs due to BRDC, indicating that these two SV are major physiological determinants of economic losses associated with BRDC. Accordingly, it is assumed that an amelioration of maximal ventilation and vital capacity could result in increased resistance to BRDC in calves. [less ▲]

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See detailSpirometric performance in Belgian Blue calves: II. Analysis of environmental factors and estimation of genetic parameters.
Bureau, Fabrice ULg; Michaux, C.; Coghe, J. et al

in Journal of Animal Science (2001), 79(5), 1162-1165

Genetic parameters and environmental effects for spirometric variables (SV) in calves were estimated using 734 Belgian Blue calves (15 to 297 d of age), sired by 20 AI bulls. For each calf, the following ... [more ▼]

Genetic parameters and environmental effects for spirometric variables (SV) in calves were estimated using 734 Belgian Blue calves (15 to 297 d of age), sired by 20 AI bulls. For each calf, the following SV were measured: 1) the average ventilation (l/min) recorded during the 15 s of maximal ventilatory changes induced by lobeline administration (0.25 mg/kg, i.v.) (15-s MV(L)); 2) the vital capacity, and the maximal peak expiratory and inspiratory flows recorded after lobeline administration; and 3) the ventilatory reserve (15-s MV(L) - ventilation at rest). Analysis of environmental factors showed age of calf, herd, sex, and vaccination status had significant effects on SV. A sire model and a multiple-trait derivative-free REML procedure were used to estimate genetic parameters for SV, body weight, and muscling score. Heritabilities for SV ranged from 0.28 +/- 0.11 to 0.44 +/- 0.16. Genetic correlations among SV varied from 0.76 to 0.98 and environmental correlations from 0.69 to 0.80. Genetic correlations of SV with body weight (0.25 to 0.56) and with muscling score (0.21 to 0.76) were positive, as were environmental correlations of SV with body weight (0.44 to 0.70) and muscling score (0.09 to 0.25). These results suggest that selection may improve SV without impairing other traits of economic importance. [less ▲]

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See detailLa capacité ventilatoire des veaux Blanc-Bleu Belges : relation avec la résistance aux pathologies respiratoires
Jacqmot, Olivier ULg; Bureau, Fabrice ULg; Dorts, T. et al

in Sixième Carrefour des Productions Animales : La Sélection Animale au Service de la Société (2001)

Les performances spirométriques ont un effet sur la morbidité, la mortalité et le coût des maladies respiratoires dans l'espèce bovine. Les veaux Blanc-Bleu Belge se distinguant des autres par de ... [more ▼]

Les performances spirométriques ont un effet sur la morbidité, la mortalité et le coût des maladies respiratoires dans l'espèce bovine. Les veaux Blanc-Bleu Belge se distinguant des autres par de meilleures performances spirométriques sont avantagés du point de vue fonctionnel respiratoire; ils sont plus résistants aux pathologies respiratoires. Parmi les variables, ce sont la capacité ventilatoire et la ventilation maximale qui sont les plus importantes pour améliorer la résistance aux maladies respiratoires. Ces variables sont héritables et cela sans diminution du gain de poids ni du développement musculaire de ces animaux [less ▲]

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See detailMechanisms of inflammation in equine airways
Lekeux, Pierre ULg; Bureau, Fabrice ULg; Art, Tatiana ULg et al

in Proceedings : 3er Congreso Iberoamericano de Veterinarios Especializados en Equinos, Montevideo (2001)

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See detailInflammation des voies respiratoires chez les équidés
Lekeux, Pierre ULg; Bureau, Fabrice ULg

in Proceedings : Congrès de l'Association Vétérinaire Equine Française (AVEF) "Médecine & Chirurgie au quotidien" (2001)

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See detailMécanismes de l'inflammation subclinique de la glande mammaire
Lekeux, Pierre ULg; Boulanger, D.; Boutet, Philippe ULg et al

in Proceedings : Congrès de la Société française de Buiatrie "Actualités en Buiatrie" (2001)

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See detailNf-Kappab Activation in Response to Toxical and Therapeutical Agents: Role in Inflammation and Cancer Treatment
Bours, Vincent ULg; Bonizzi, Giuseppina; Bentires-Alj, Mohamed et al

in Toxicology (2000), 153(1-3), 27-38

The NF-kappaB transcription factor is ubiquitously expressed and controls the expression of a large number of genes. Experimental data clearly indicate that NF-kappaB is a major regulator of the ... [more ▼]

The NF-kappaB transcription factor is ubiquitously expressed and controls the expression of a large number of genes. Experimental data clearly indicate that NF-kappaB is a major regulator of the inflammatory reaction by controlling the expression of pro-inflammatory molecules in response to cytokines, oxidative stress and infectious agents. We demonstrated that NF-kappaB activation by IL-1beta follows three distinct cell-specific pathways. Moreover, our studies indicated that in one model of inflammatory diseases, horse recurrent airway obstruction (RAO), the extent of NF-kappaB basal activity correlates with pulmonary dysfunction. Another role of NF-kappaB activity protects cancer cells against apoptosis and could participate in the resistance to cancer treatment. However, we did not observe any increased cytotoxicity after treatment with anticancer drugs or TNF-alpha of cells expressing a NF-kappaB inhibitor. Therefore, we can conclude that the inhibition of apoptosis by NF-kappaB is likely to be cell type and stimulus-dependent. Further studies are required to determine whether NF-kappaB could be a target for anticancer treatments. [less ▲]

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See detailMechanisms of Persistent Nf-Kappa B Activity in the Bronchi of an Animal Model of Asthma
Bureau, Fabrice ULg; Delhalle, Sylvie; Bonizzi, Giuseppina et al

in Journal of Immunology (2000), 165(10), 5822-5830

In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent ... [more ▼]

In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent inflammatory gene expression is persistent in asthmatic bronchi, even after allergen eviction. In the present report we used bronchial brushing samples (BBSs) from heaves-affected horses (a spontaneous model of asthma) to elucidate the mechanisms by which NF-kappaB activity is maintained in asthmatic airways. NF-kappaB activity was high in granulocytic and nongranulocytic BBS cells. However, NF-kappaB activity highly correlated to granulocyte percentage and was only abrogated after granulocytic death in cultured BBSs. Before granulocytic death, NF-kappaB activity was suppressed by simultaneous addition of neutralizing anti-IL-1beta and anti-TNF-alpha Abs to the medium of cultured BBSs. Surprisingly, IkappaB-beta, whose expression is not regulated by NF-kappaB, unlike IkappaB-alpha, was the most prominent NF-kappaB inhibitor found in BBSs. The amounts of IkappaB-beta were low in BBSs obtained from diseased horses, but drastically increased after addition of the neutralizing anti-IL-1beta and anti-TNF-alpha Abs. These results indicate that sustained NF-kappaB activation in asthmatic bronchi is driven by granulocytes and is mediated by IL-1beta and TNF-alpha. Moreover, an imbalance between high levels of IL-1beta- and TNF-alpha-mediated IkappaB-beta degradation and low levels of IkappaB-beta synthesis is likely to be the mechanism preventing NF-kappaB deactivation in asthmatic airways before granulocytic death. [less ▲]

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